Biology subjects

Grabauskas, T.

Publications and source records attributed to Grabauskas, T..

2 recordsLinked to original sources

bioRxiv2025

CMV reshapes lymphoid immunity in aging: a single-cell atlas with predictive modeling

Cytomegalovirus (CMV) is a common herpesvirus that establishes lifelong latency and becomes increasingly prevalent with age. We systematically characterized CMV-associated immune remodeling by analyzing six human cohorts (two newly built) using single-cell RNA sequencing, T cell receptor (TCR) sequencing, and flow cytometry. Beyond the well-known expansion of CD4/CD8 TEMRA, adaptive NK, and {gamma}{delta} T cells, CMV(+) adults exhibited increased frequencies of GZMK CD8 T cells and atypical B cells, alongside a reduction of CD56dim NK cells. Longitudinal profiling of an individual who seroconverted revealed rapid CMV-driven shifts in circulating immune cell frequencies. Single-cell TCR data analyzed using a large database of CMV-associated clones combined with predictive modelling (CMVerify), identified novel CMV-specific clonal expansions reproduced across two independent cohorts. In the CD8 lineage, CMV-specific clones were enriched in GZMK CD8 and CD8 TEMRA cells, while in the CD4 lineage, Th1 cells showed clonal expansion alongside CD4 TEMRA cells. This integrative study revealed how latent CMV alters the cellular and clonal landscape, defining GZMK CD8 and Th1 cells as newly recognized elements of response to CMV in humans.

immunology↗

bioRxiv2020

Aberrant gliogenesis and excitation in MEF2C autism patient hiPSC-neurons and cerebral organoids

MEF2C has been shown to be a critical transcription factor for neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Here, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found an aberrant micro-RNA-mediated gliogenesis pathway that contributes to decreased neurogenesis. We also demonstrate network-level hyperexcitability in neurons, as evidenced by excessive synaptic and extrasynaptic activity contributing to excitatory/inhibitory (E/I) imbalance. Notably, the extrasynaptic NMDA receptor antagonist, NitroSynapsin, corrects this aberrant electrical activity associated with abnormal phenotypes. During neurodevelopment, MEF2C regulates many ASD-associated gene networks suggesting that our approach may lead to personalized therapy for multiple forms of ASD. One sentence summaryAutism-like MEF2C+/- patient hiPSC models show miRNA-mediated overproduction of astrocytes and hyperactivity of neurons.

neuroscience↗